NCT06420349

NXP800 for the Treatment of Patients With Advanced or Metastatic Cholangiocarcinoma

Phase 1b Study of the Novel GCN2 Kinase Activator NXP800 in Patients With Advanced Cholangiocarcionoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, best dose, and effectiveness of NXP800 in treating patients with cholangiocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). NXP800 inhibits a pathway called the heat shock factor 1 (HSF1) pathway. The inhibition of this pathway inhibits proliferation, migration, survival, and metastasis in susceptible tumor cells. Overexpressed, amplified and/or overactivated in many cancer cells, HSF1 activates a set of genes that play a key role in tumor initiation, progression and metastasis. Inhibiting this pathway may in turn inhibit tumor initiation, progression, and/or metastasis. Giving NXP800 may be safe, tolerable and/or effective in treating patients with advanced or metastatic cholangiocarcinoma.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD)/recommended phase 2 dose for heat shock factor 1 pathway inhibitor NXP800 (NXP800). SECONDARY OBJECTIVES: I. To determine the toxicity profile of NXP800. II. To determine the best response for NXP800 using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. III. To estimate the overall survival (OS) for NXP800. IV. To estimate the progression-free survival (PFS) for NXP800. EXPLORATORY OBJECTIVES: I. To evaluate transcriptomic features associated with sensitivity, resistance and pharmacodynamic effect of NXP800 using serial ribonucleic acid-sequencing (RNA-Seq). II. To assess tumor evolution with NXP800 using serial whole genome-sequencing (Seq). III. To assess tumor evolution with NXP800 using serial circulating tumor deoxyribonucleic acid (DNA) (ct-DNA). IV. To estimate tumor marker response using serial CA19-9/carcinoembryonic antigen (CEA). OUTLINE: This is a dose de-escalation study of NXP800 followed by a dose-expansion study. Patients receive NXP800 orally (PO) according to assigned treatment schedule. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) at baseline and on study. Patients may optionally undergo ultrasound-guided tumor biopsy and/or collection of blood samples on study and during follow up. After completion of study treatment, patients are followed up every 6 months until progressive disease or death for up to 3 years.

Conditions

• Advanced Cholangiocarcinoma
• Metastatic Cholangiocarcinoma
• Refractory Cholangiocarcinoma
• Stage III Hilar Cholangiocarcinoma AJCC v8
• Stage III Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IV Hilar Cholangiocarcinoma AJCC v8
• Stage IV Intrahepatic Cholangiocarcinoma AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT
BIOLOGICAL	Heat Shock Factor 1 Pathway Inhibitor NXP800	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET
PROCEDURE	Ultrasound-Guided Biopsy	Undergo ultrasound-guided tumor biopsy

Timeline

• Start date: 2024-05-31
• Primary completion: 2025-08-12
• Completion: 2025-09-09
• First posted: 2024-05-20
• Last updated: 2025-12-22

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study